A closed loop, glucose sensing, and insulin responsive system could dramatically improve treatment options for insulin dependent diabetics. Current artificial systems, however, lack the ability to provide this precise control. Clinical islet transplantation, the intrahepatic loading of allogeneic islets, shows the potential to provide this intimate control, by transplanting the very cells with this inherent glucose sensing/insulin secreting capacity. Limiting islet transplantation, however, is the significant loss and dysfunction of islets following implantation, due to the poor engraftment environment and significant immunological attack. We have sought to address these roadblocks by developing two platform technologies for optimizing islet environment and blocking immune attack: 1) three dimensional scaffolds;and 2) micron thick conformal biomaterial coatings. Our long term goal is to converge these two platforms to reduce the islet load required for efficacy, minimize islet loss following transplant, and to dramatically reduce the need for systemic immunosuppression. In this proposal, we seek to optimize these promising platforms at the scale necessary for translation to the clinic. We seek to develop technologies to improve the efficiency and consistency of our macroporous scaffolds, as well as our conformal coating method. To achieve these aims, we seek to fabricate equipment and optimize protocols, as well as evaluate the efficacy of these platforms in pre-clinical models of diabetes. Our preliminary data strongly support the feasibility of this proposal, as well as our strategic collaborations with the Diabetes Research Institute at the University of Miami. Accomplishment of our aims will dramatically enhance the efficacy of islet transplantation, thereby providing a significant enhancement in treatment options for insulin dependent diabetics. PUBLIC HEALTH RELEVANCE: The development of treatment options for insulin-dependent diabetics that provide a highly regulated glucose sensing and insulin secreting closed loop system could result in dramatic improvements in quality of life, as well as a substantial decrease in disease management complications. We seek to develop a cell-based, bioartificial pancreas system that mimics the native pancreas, by providing an optimal three dimensional environment to the transplanted cells, as well as immunoprotection. This project seeks to translate our promising platform to the clinic through the scale up of our current fabrication methods, as well as initiating pre- clinical testing. We believe these studies are highly relevant to the mission of the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) and are designed to result in a significant impact on public health.